systems pharmacology approach to uncontrolled pediatric asthma

Conditions: Pediatric Asthma; Uncontrolled Asthma

Summary: background: asthma is a heterogeneous respiratory disease and the most common chronic disease in children. a small subset of children has continuous poor asthma control despite appropriate adherence to asthma medication. there is a clinical need to identify these children as early as possible to optimize treatment and/or to find therapeutic alternatives. therefore, the "systems pharmacology approach to uncontrolled pediatric asthma" (syspharmpedia) study was set up. objective: to establish a cohort of pediatric moderate-to-severe uncontrolled and controlled patients with asthma in order to investigate pathophysiological mechanisms underlying uncontrolled moderate-to-severe asthma in children on maintenance treatment, using a multi-omics systems medicine approach. methods: in this multicenter observational case-control study, moderate-to-severe asthmatic children (n=145, age 6-17 years), were included in specialized hospitals in four european countries (netherlands, germany, spain and slovenia). recruited subjects were selected based on good asthma control (controlled asthmatics, n=54) or poor asthma control / recurrent exacerbations (uncontrolled asthmatics, n=91). comprehensive details concerning demographics, current and past patient/family history and clinical characteristics were collected. in addition, systems-wide omics layers, including epi(genomics), transcriptomics, microbiome, proteomics and metabolomics will be evaluated from multiple collected, relatively non-invasive, samples of from the recruited individuals, such as: blood, feces, saliva, nasal swabs and exhaled breath. follow-up visits were performed 6 and 12 months after inclusion.


Eligibility criteria:
inclusion criteria: general: * between 6-17 years of age * doctor diagnosis of asthma in addition to the general criteria, a case with uncontrolled asthma (case group a) should meet: * asthma treatment global initiative of asthma (gina) step 3 or higher ≥ 1of the following criteria (based on the guideline 'childhood asthma' of the section paediatric pulmonology of the dutch society of paediatricians, 2007): * frequent exacerbations requiring ocs use (≥1 in the past year) and/or * severe exacerbations requiring hospitalization or er visits in the past year and/or * acq/act scores indicating uncontrolled asthma in addition to the general criteria, a case with an acute exacerbation (case group b) should meet: * asthma treatment global initiative of asthma (gina) step 2 or higher * current severe asthma exacerbation requiring hospitalization in addition to the general inclusion criteria, a control (controlled asthma) should meet the following criteria: * asthma treatment global initiative of asthma (gina) step 3 or higher * lack of severe exacerbations requiring ocs use or hospitalizations or er visits in the past year * acq/act scores indicating well controlled asthma or few reported asthma symptoms during asthma checks in the past year. exclusion criteria: * recent use of a course of antibiotics (\< 1 month). this will affect the microbiome analyses. a patient can be re-screened 1 month after the use of the antibiotic treatment has finished.

Keywords: systems pharmacology omics